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TY - JOUR
T1 - Mutational change of CTX-M-15 to CTX-M-127 resulting in mecillinam resistant Escherichia coli during pivmecillinam treatment of a patient
AU - Nielsen, Karen Leth
AU - Hansen, Katrine Hartung
AU - Nielsen, Jesper Boye
AU - Knudsen, Jenny Dahl
AU - Schønning, Kristian
AU - Frimodt-Møller, Niels
AU - Hertz, Frederik Boëtius
AU - Jansåker, Filip
N1 - © 2019 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.
PY - 2019/12
Y1 - 2019/12
N2 - Pivmecillinam (amdinocillin pivoxil) is the recommended first-choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. The frequency of mutation to mecillinam (MEC) resistance is described as high in vitro; however, treatment of UTI has a good clinical response and prevalence of mecillinam resistance in Escherichia coli remains low despite many years of use. We describe occurrence of in vivo mecillinam resistance in a clinical isolate of ESBL-producing E. coli following pivmecillinam treatment. The identified phenotypic differences in the mecillinam resistant isolate compared with the original mecillinam susceptible isolate were a full-length LPS with O-antigen (O25), mecillinam resistance and a lower MIC for ceftazidime. Regarding genotype, the resistant isolate differed with a mutation in blaCTX-M-15 to blaCTX-M-127 , loss of a part of a plasmid and a genomic island, respectively, and insertion of a transposase in wbbL, causing the rough phenotype. The observed mecillinam resistance is expected to be caused by the mutation in blaCTX-M-15 with additional contribute from the serotype shift. We continue to recommend the use of pivmecillinam as first-line treatment for UTI.
AB - Pivmecillinam (amdinocillin pivoxil) is the recommended first-choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. The frequency of mutation to mecillinam (MEC) resistance is described as high in vitro; however, treatment of UTI has a good clinical response and prevalence of mecillinam resistance in Escherichia coli remains low despite many years of use. We describe occurrence of in vivo mecillinam resistance in a clinical isolate of ESBL-producing E. coli following pivmecillinam treatment. The identified phenotypic differences in the mecillinam resistant isolate compared with the original mecillinam susceptible isolate were a full-length LPS with O-antigen (O25), mecillinam resistance and a lower MIC for ceftazidime. Regarding genotype, the resistant isolate differed with a mutation in blaCTX-M-15 to blaCTX-M-127 , loss of a part of a plasmid and a genomic island, respectively, and insertion of a transposase in wbbL, causing the rough phenotype. The observed mecillinam resistance is expected to be caused by the mutation in blaCTX-M-15 with additional contribute from the serotype shift. We continue to recommend the use of pivmecillinam as first-line treatment for UTI.
KW - Escherichia coli
KW - LPS
KW - mecillinam
KW - metabolism
KW - mutation
KW - O-antigen
KW - Pivmecillinam
KW - resistance
KW - serotype
KW - whole-genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85073931705&partnerID=8YFLogxK
U2 - 10.1002/mbo3.941
DO - 10.1002/mbo3.941
M3 - Journal article
VL - 8
SP - 1
EP - 4
JO - MicrobiologyOpen
JF - MicrobiologyOpen
SN - 2045-8827
IS - 12
M1 - e941
ER -
ID: 58060601